Proper integration of multiple senses is critical for providing a coherent perception of the environment. Cross-modal relay of sensory information is not only critical for multisensory integration, but provide substrates for cross-modal compensation when losing a sensory modality. For example, in blind individuals cross-modal compensation is observed as enhanced functionality in the remaining senses as well as recruitment of visual areas by Braille reading. While cross-modal plasticity is largely beneficial to blind individuals, it poses a challenge when attempting to recover function by clinical interventions. For instance, the success of recovering hearing by cochlear implants is reported to inversely correlate with the extent of cross-modal sensory compensation. It is likely that recovery of vision will encounter similar obstacles. Most studies of cross-modal plasticity focuses on systems level analyses, hence cellular and circuit level mechanistic understanding is quite limited. We previously reported that depriving rodents of vision by dark-rearing not only alters synaptic transmission in primary visual cortex (V1), but also produces opposite changes in primary auditory cortex (A1). In particular, we observed an increase in excitatory synaptic transmission in the superficial layers of V1, but a decrease in excitatory synaptic transmission in the superficial layers of A1 following dark-rearing. While our data suggest that visual deprivation can globally alter excitatory synaptic transmission across different primary sensory cortices, it is unclear how these changes affect cortical function. In this proposal, we will test the hypothesis that visual deprivation-induced decrease in excitatory synaptic transmission alters the receptive field properties of A1 neurons. We will test our hypothesis by combining in vitro whole-cell recordings to assess specific circuit properties of layer 2/3 neurons in A1, and in vivo single unit recordings of these neurons from awake mice. Specifically, we will determine whether visual deprivation alters the functional circuitry (Aim 1) and the receptive field properties (Aim 2) of layer 2/3 neurons in A1. Furthermore, we will investigate whether the cross-modal synaptic changes are responsible for altering receptive field properties in A1 (Aim 3). Results from our project will provide a cellular and circuit level mechanistic understanding of how loss of vision affects the functionality of A1 neurons. In addition, it will provide evidence that cross-modal changes occur in primary sensory cortices. PUBLIC HEALTH RELEVANCE: Blind individuals display enhance functionality in the remaining senses, such as better sound localization and discrimination. We will examine how loss of vision affects the function of primary auditory cortex, an area of the brain involved in sound processing. Results from our work will benefit the development of therapeutics for recovering vision, as extensive sensory compensation is known to impede the recovery of the lost sense.